Abstract

Heterologous prime-boost regimens utilizing BCG as a prime vaccine probably represent the best hope for the development of novel tuberculosis (TB) vaccines. In this study, we examined the immunogenicity and protective efficacy of DNA vaccine (pcD685A) expressing the fusion protein of Ag85A and ESAT-6 (r685A) and its booster effects in BCG-immunized mice. The recombinant r685A fusion protein stimulated higher level of antigen-specific IFN-γ release in tuberculin skin test- (TST-) positive healthy household contacts of active pulmonary TB patients than that in TST-negative population. Vaccination of C57BL/6 mice with pcD685A resulted in significant protection against challenge with virulent Mycobacterium tuberculosis H37Rv when compared with the control group. Most importantly, pcD685A could act as a BCG booster and amplify Th1-type cell-mediated immunity in the lung of BCG-vaccinated mice as shown the increased expression of IFN-γ. The most significant reduction in bacterial load of both spleen and lung was obtained in mice vaccinated with BCG prime and pcD685A DNA booster when compared with BCG or pcD685A alone. Thus, our study indicates that pcD685A may be an efficient booster vaccine against TB with a strong ability to enhance prior BCG immunity.

Highlights

  • Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a leading infectious killer worldwide [1]

  • We evaluated the immune responses generated against DNA vaccine expressing the fusion protein of ESAT6 and Ag85A (r685A) and the immunogenicity of r685A fusion protein in tuberculin skin test- (TST-) positive healthy populations

  • The genes of ESAT-6 and Ag85A were first amplified by PCR and M. tuberculosis H37Rv genomic DNA as the template (Figure 1)

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Summary

Introduction

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a leading infectious killer worldwide [1]. The emergence and spread of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) and coinfection with TB/HIV pose serious challenges to effective TB control [2]. M. bovis BCG is currently the only available vaccine against TB, with over 120 million doses administered annually [3]. BCG immunization provides protection against severe forms of TB in children, including tuberculous meningitis and miliary TB [4]. BCG induced-protection lasts less than 15 years because antituberculous protective immunity wanes gradually after the initial immunization [5]. Developing new, more effective vaccines and immunization strategies aimed to boost waning BCG-induced protective responses, is urgently needed

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